Almeqdadi, Mohammad, Yueh, Brian, Paredes, Jenny, Akadri, Mubarak, Spagnardi, Marzia, Chung, Charlie, Martello-Rooney, Laura, Beyaz, Semir (May 2021) EXPLORING THE RACIAL DISPARITIES OF COLON CANCER OUTCOMES IN THE SETTING OF OBESITY. In: Digestive Disease Week 2021.
Abstract
Background: African Americans (AA) have higher incidence and mortality from colon cancer compared to Caucasian Americans (CA). The mechanisms that drive this difference are not well understood. Genetic, environmental and socioeconomic factors play important roles in colon cancer pathogenesis and each may contribute to this disparity. One of the important factors that may influence different aspects of colon cancer is obesity. Obesity as a lowgrade inflammatory state creates changes in the epigenetic and metabolic landscape in ways that promote the initiation and progression of colon cancer. In this study, we use a multipronged approach in exploring potential contributory elements that may explain the disproportionate burden of colon cancer in AA patients. Methods: IRB-approved prospective collection of samples from colon cancer patients undergoing surgical resection from the two cohorts (AA/CA, Normal/Obese) were assembled and clinically annotated. The samples included tumor and adjacent non-tumor tissues and blood for plasma isolation (AA=30, CA=23). Tumor tissue DNA was isolated and mutation analysis was acquired via PanelSeq, which included 60 commonly mutated genes in colon cancer. Plasma samples will be sent for metabolomic analysis. The tumor tissue samples were used for stem cell isolation and were cultured as 3-dimensional organoid cultures. Finally, tumor organoids will be transplanted into NOD scid gamma mice using colonoscopy-assisted orthotopic xenotransplantation method that we developed. Results: DNA mutation analysis showed widely different mutational landscape across the samples (Figure 1). Notable mutations included common colon cancer drivers such as APC and KRAS, as well as mismatch repair mutations such as MLH1 and PMS1. AA and CA colon tumor organoids exhibited no significant differences in proliferation (Figure 2). Metabolomics analysis and orthotopic transplantation to be performed. Conclusions: Colon cancer is the third leading cause of cancer death in the U.S. The incidence and mortality are worse in AA patients compared to CA patients. Moreover, obesity is a major modifiable risk factor that plays an important role in the pathogenesis of colon cancer. Here we show that the mutational landscape of colon cancer is distinct between the two cohorts (AA vs. CA) and BMIs (Normal vs. Obese). The metabolomics data is pending but we expect to see differences. Finally, we developed in vitro colon tumor organoid cultures derived from AA patient samples that can be utilized for mechanistic experiments. Tumor organoids will also be used for orthotopic xenotransplantation in our model for colon cancer. To our knowledge, this has never been done with samples from AA patients and opens the door for future work in exploring the pathogenesis of the heightened colon cancer incidence and mortality in this underrepresented population.
| Item Type: | Conference or Workshop Item (Paper) |
|---|---|
| Subjects: | diseases & disorders > cancer > cancer types > colon cancer diseases & disorders > cancer > cancer types > colon cancer diseases & disorders > cancer > drugs and therapies > patient outcomes |
| CSHL Authors: | |
| Communities: | CSHL labs > Beyaz lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | May 2021 |
| Date Deposited: | 21 Jun 2021 18:01 |
| Last Modified: | 21 Jun 2021 18:02 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/40220 |
Actions (login required)
 |
Administrator's edit/view item |